The brain has an amazing ability to flexibly engage different functional networks based on the demands of a constantly changing environment. Sometimes forces acting on an intrinsic, baseline environment are transient, such as the dynamic cognitive demands of daily life. At other times they are longer term, and occasionally permanent, such as the changes that occur due to aging, brain damage, or psychiatric disorders. Recently there has been a focus on measuring the intrinsic functional connectivity of networks of brain regions during rest using functional MRI (fMRI). The application of graph theoretical tools taken from the field of mathematics to these intrinsic brain networks allows for the quantification of network properties, such as the degree to which groups of brain regions separate themselves into largely independent networks (or modules), and the identification of the role of individual brain regions, such as whether a region is integral for communication across multiple brain regions and networks, or whether a region limits its interactions to a small subset of brain regions within a single network. This proposal aims to extend this characterization of intrinsic brain networks to other contexts to assess the brain's potential for plasticity in different contexts. The proposed research, therefore, will investigate both the reconfiguration of global brain organization and the changing roles of individual brain regions from intrinsic network configuration in two different contexts: 1) disruption of functioning due to focal brain lesions, and 2) specific cognitive demands due to administration of different conditions of a cognitive task. METHOD: This research proposal will apply state-of-the-art methodologies and analyses to address the specific aims. The first experiment will analyze data that was collected from patients with focal brain lesions and age-matched healthy controls to assess the extent of network reconfiguration after brain damage. I hypothesize that adaptive network reconfiguration will occur if the role of intact tissue within the network that sustained te brain damage changes to be more similar to the role that the damaged tissue had in healthy, intrinsic brain organization. I predict that within-network adaptation is a more accurate manner of characterizing compensatory changes in brain organization than is focusing purely on intact tissue anatomically close to the damaged tissue (i.e., perilesional tissue) or on intact tissue in homologous regions in the undamaged (i.e., contralesional) hemisphere. The second experiment will examine the brain's ability to reconfigure in different cognitive contexts in healty young adults. I hypothesize that adaptive network reconfiguration will occur by changing network organization toward a single context-specific network made up of cognitively relevant regions and connections across separate intrinsic networks. Critically, the adaptive nature of this reconfiguration will be assessed by relating behavioral performance to the degree to which regions integral for task performance are important for communication within that context-specific network. PUBLIC HEALTH RELEVANCE: This research will further knowledge of the adult brain's potential for plasticity due to changes to its intrinsic, baseline environment, including brain damage, aging, and the cognitive demands of a dynamically altering environment. It is proposed that a potential mechanism underlying neural plasticity is the changing role of individual brain regions to adapt to the demands of the current environment and that this plasticity results in reconfiguration that is adaptive (as assessed by network organization close to a healthy state after brain damage and a relationship between reconfiguration and performance in healthy networks during cognitive performance). Crucially, this increased knowledge can lead to treatments involving cognitive training and rehabilitation in cognitively impaired or brain-damaged individuals that target adaptive reconfiguration.